RESUMO
Myocardial ischemia initiates a chain of pathological conditions leading to cardiomyocyte death. Therefore, pharmacological treatment to stop ischemia-induced damage is necessary. Fibrates, have been reported to decrease inflammatory markers and to modulate the renin-angiotensin system (RAS). Our aim was to explore if clofibrate treatment, administered one week after myocardial event, decreases MI-induced cardiac damage. Wistar rats were assigned to: 1. Sham or 2. Coronary artery ligation (MI). Seven days after, rats were subdivided to receive vehicle (V) or clofibrate [100 mg/kg (C)] daily for 7 days. Blood samples and left ventricle were analyzed. RAS components [angiotensin II, angiotensin converting enzyme (ACE), and AT1-receptor] decreased in MI-C compared to MI-V, while [Ang-(1-7), bradykinin, ACE-2, and AT2-receptor] raised in response to clofibrate treatment. Oxidative stress markers increased in MI-V rats, a profile reverted in MI-C rats. Nitric oxide (NO) pathway (Akt, eNOS, and NO) exhibits a lower participation in MI-V, but clofibrate raised NO-pathway components and its production. MI-induced fibrosis and structural damage was also improved by clofibrate-treatment. In conclusion, clofibrate administration to 7 days MI-rats exerts an antioxidant, pro-vasodilator expression profile, and anti-fibrotic effect suggesting that PPARα activation can be considered a therapeutic target to improve cardiac condition posterior to ischemia.
Assuntos
Clofibrato/administração & dosagem , Clofibrato/farmacologia , Ventrículos do Coração/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/metabolismo , Miocárdio/patologia , Óxido Nítrico/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Fibrose , Ventrículos do Coração/patologia , Masculino , Isquemia Miocárdica/patologia , Estresse Oxidativo/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Ratos Wistar , Receptor Tipo 1 de Angiotensina/metabolismo , Fatores de TempoRESUMO
Prevalence of metabolic syndrome and progression of nephropathy depend on sex. We examined a protective effect of estradiol against nephropathy in metabolic syndrome through the modulation of the arachidonic acid metabolism by activating the 5-lipoxygenase and cytochrome p450 4A pathways. 28 female Wistar rats were divided into four groups of seven animals each: control, intact metabolic syndrome, ovariectomized metabolic syndrome, and metabolic syndrome ovariectomized plus estradiol. Blood pressure, body weight, body fat, triglycerides, insulin, HOMA-index, albuminuria, and TNF-α were increased in ovariectomized metabolic syndrome rats (p < 0.001). The perfusion pressure in isolated kidneys of ovariectomized metabolic syndrome rats in presence of 4 µg of arachidonic acid was increased. The inhibitors of the arachidonic acid metabolism Baicalein, Miconazole, and Indomethacin in these rats decreased the perfusion pressure by 57.62%, 99.83%, and 108.5%, respectively and they decreased creatinine clearance and the arachidonic acid percentage. Phospholipase A2 expression in the kidney of ovariectomized metabolic syndrome rats was not modified. 5-lipoxygenase was increased in metabolic syndrome ovariectomized rats while cytochrome p450 4A was decreased. In conclusion, the loss of estradiol increases renal damage while the treatment with estradiol benefits renal function by modulating arachidonic acid metabolism through the 5-lipoxygenase and cytochrome p450 4A pathways.
RESUMO
1. The aim of the present study was to analyze histological and stereological changes in the tubular compartment in Gallus domesticus testes, as well as the variations in the number and size of their cells, from the start of morphological differentiation of the gonads (8-d chick-embryo) until the adult reproductive stage (28 weeks old). 2. In embryonic chick testes, the total volume occupied by the interstitial tissue is greater than that occupied by the tubular compartment, but in the post-hatched chick the total volume of tubular compartment exceeds that of the interstitial tissue. 3. From day 1 until 28 weeks of age, the seminiferous tubules increased in total volume, diameter, and epithelial height, which was directly related to the increase in the number of Sertoli and germ cells and the size of Sertoli cells. 4. In the testes of one-day- and 6-week-old chicks, Sertoli cells were the most abundant cell type in the seminiferous tubules due to hyperplasia, but in 28-week-old birds the germ cells were the most abundant cell type. Hypertrophy rather than hyperplasia of Sertoli cells appears to be responsible for the increase in the total volume of seminiferous tubules. 5. There are marked age-dependent changes in the tubular compartment of chick testes that help to understand the histological and stereological events occurring during normal development.